Quantification of JC Virus DNA in the Cerebrospinal Fluid of Patients with Human Immunodeficiency Virus–Associated Progressive Multifocal Leukoencephalopathy—A Longitudinal Study

Abstract

In progressive multifocal leukoencephalopathy (PML) the JC virus (JCV) load in the cerebrospinal fluid (CSF) is discussed as a parameter for disease progression. To investigate the evolution of viral shedding into the CSF, the JCV DNA concentration was quantified by competitive polymerase chain reaction (PCR) in multiple CSF samples from prior to and during an unsuccessful intrathecal salvage therapy in 2 human immunodeficiency virus-infected patients with biopsy-proven PML. With continuous clinical progression the virus load varied considerably intra- and interindividually, ranging from nondetectable to 1.2x108 genome equivalents/10 microliter CSF. Whereas an overall increase during progressive disease was confirmed, the virus burden was either constant or fluctuated irregularly during the intermediate stage of disease. This shows a variability of viral shedding during active disease that must be taken into account when the JCV load is measured by quantitative PCR for both the diagnosis of PML and monitoring under investigational treatment.

Molecular Methods for Diagnosis of Viral Encephalitis

“…A potential correlation between the JCV viral load in CSF and the PML prognosis has also been investigated by using quantitative PCR techniques (76,81,88,89,133,225,226,258). In a recent study, CSF samples from 12 patients with PML were noted to have wide variations in JCV load (Ͼ6 log units), with values of Ͼ4.7 log units associated with shorter patient survival time.…”

Latent and Persistent Polyomavirus Infection

“…Nevertheless, persistent infection remains asymptomatic, probably indicating that the actual number of infected cells and the virus load is low and difficult to detect. In contrast, polyomavirus disease in the CNS correlates strongly with viral presence in CSF (Dörries, 1996;Dörries et al, 1998;Eggers et al, 1999;Vallbracht et al, 1993;Weber and Major, 1997). Consequently, detection of JCV DNA in CSF can serve as an indirect marker for activation of a persistent virus infection.…”

Progressive Multifocal Leukoencephalopathy in an HIV Patient

“…There is also some evidence that vital prognosis (lesion progression and death) and the speed of the onset correlate directly with JCV CSF count [3,20]. Our patient had no JCV detected in the first determinations.…”